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Orphanet Journal of Rare Diseases

BioMed Central

Open Access

Review

Congenital Cataracts – Facial Dysmorphism – Neuropathy

Luba Kalaydjieva*

Address: Western Australian Institute for Medical Research and Centre for Medical Research, The University of Western Australia, Hospital Avenue, WA 6009 Nedlands, Australia

Email: Luba Kalaydjieva* - [email protected] * Corresponding author

  • Published: 29 August 2006
  • Received: 11 July 2006

Accepted: 29 August 2006

Orphanet Journal of Rare Diseases 2006, 1:32 doi:10.1186/1750-1172-1-32

This article is available from: http://www.OJRD.com/content/1/1/32 © 2006 Kalaydjieva; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN) syndrome is a complex developmental disorder of autosomal recessive inheritance. To date, CCFDN has been found to occur exclusively in patients of Roma (Gypsy) ethnicity; over 100 patients have been diagnosed. Developmental abnormalities include congenital cataracts and microcorneae, primary hypomyelination of the peripheral nervous system, impaired physical growth, delayed early motor and intellectual development, mild facial dysmorphism and hypogonadism. Para-infectious rhabdomyolysis is a serious complication reported in an increasing number of patients. During general anaesthesia, patients with CCFDN require careful monitoring as they have an elevated risk of complications. CCFDN is a genetically homogeneous condition in which all patients are homozygous for the same ancestral mutation in the CTDP1 gene. Diagnosis is clinical and is supported by electrophysiological and brain imaging studies. The major differential diagnosis is Marinesco-Sjögren syndrome. The definitive diagnosis is molecular, based on homozygosity for the CTDP1 mutation. CTDP1 maps to 18qter and encodes a protein phosphatase whose only known substrate is the phosphorylated serine residues of the carboxy-terminal domain of the largest subunit of RNA polymerase II, indicating that CCFDN affects basic cellular processes of gene expression and developmental regulation. Families benefit from genetic counselling and predictive testing. Management includes surgical treatment of the cataracts, and rehabilitation and corrective orthopaedic surgery for the peripheral neuropathy. Thus, the most disabling manifestations, though not curable, are manageable, and allow an acceptable quality of life and everyday living. Current data indicate that patients survive well into adulthood.

Primary diagnostic criteria

• Bilateral congenital cataracts, microcornea, microphthalmos, micropupils

Disease name

Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN) syndrome

• Developmental delay

Definition/diagnostic criteria

CCFDN is a complex developmental disorder of autosomal recessive inheritance which, so far, has been found to occur exclusively in patients of Roma (Gypsy) ethnicity [1,2].
• Small stature and low weight • Hypo/demyelinating neuropathy

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• Mild facial dysmorphism • Mild hypogonadism morphism develops in late childhood and is more evident in male than in female subjects. It includes a prominent midface with a well developed nose, thickening of the perioral tissues, forwardly directed anterior dentition and hypognathism. Skeletal deformities are present in most patients, especially adults. Foot deformities, namely pes cavus or pes equinovarus with clawing of the toes, are very common. Claw hand deformity develops in the course of the disease and is observed in most adult patients. Kyphoscoliosis may develop and leads to reduced vital capacity.

Additional criteria

• Mild cognitive deficit • Cerebral and spinal cord atrophy on neuroimaging • Post-infectious rhabdomyolysis

  • • Osteoporosis
  • The most striking neurological manifestation is a symmet-

ric, distally accentuated, predominantly motor peripheral neuropathy. Motor involvement is evident in all affected subjects, including young children, and progresses to severe disability in the third decade. Loss or depression of tendon reflexes, initially in the lower limbs, is universally observed. Nerve conduction velocity is normal in early infancy and declines after age 18 months, stabilizing at ~20 m/s after 4 years [8]. Distal motor latency is increased. Sensory action potential values are of normal amplitude, suggesting a relatively uniform degree of slowing of conduction across nerve fibres, consistent with congenital hypomyelination. Neuropathological evidence of primary hypomyelination is provided by nerve biopsy studies, showing also a superimposed demyelination/remyelination and axonal degeneration increasing with age.

Epidemiology

The CCFDN mutation is particularly common among the Rudari, an endogamous, recently founded Roma population, in whom the carrier rate is around 6–7% [3,4]. In other Gypsy groups, it is ~1%. The disorder has so far been diagnosed in over 100 Roma patients, whose countries of residence reflect past and recent migrations of the affected population, as well as access to healthcare and awareness of this syndrome among health care providers. Most known affected subjects belong to the traditional Roma population of Balkan and Central European countries (Bulgaria, Romania, Serbia, Greece, Hungary, the Czech Republic), or are recent migrants to Austria and Germany; with cases also diagnosed in Italy, France, The Netherlands, USA and Canada. CCFDN should be considered as the most likely diagnosis in infants of Roma ethnicity presenting with congenital cataracts.
Other, less consistent, neurological abnormalities include bilaterally extensor plantar responses, choreiform movements, mild ataxia and upper limb postural tremor. Abnormal electroencephalographic recordings are a very common finding, with usually diffuse slow wave activity. Brain and spinal cord abnormalities have been identified in many patients by magnetic resonance imaging (MRI) examination [2]. The changes appear to be age-related and may not be detectable in affected children. The abnormalities include diffuse cerebral atrophy with enlargement of the lateral ventricles, and spinal cord atrophy sometimes also involving the medulla oblongata. A recent study, using diffusion tensor MRI in a small group of CCFDN patients revealed a higher apparent diffusion coefficient and lower fractional anisotropy in the vermis and medulla oblongata, suggesting axonal loss in these parts of the brain [8]. Mild non-progressive cognitive deficit is often present; however, its assessment should take into account the visual impairment, as well as possible social deprivation of the affected subjects.

Clinical description

The CCFDN phenotype is complex and affects multiple organs and tissues, mostly during intra-uterine development. Detailed descriptions of the clinical manifestations are available [2,5-7].

Prenatal eye development is invariably affected and the congenital cataracts are the first CCFDN manifestation, recognisable in early infancy. The cataracts are bilateral and are characterised by anterior or posterior cortical dense opacities with clouding of the adjacent part of the lens nucleus or total cataracts involving the whole lens. These are accompanied by microcornea, microphthalmos and micropupils. Additional ophthalmological features include floppy eyelids and long and dense eyelashes, nystagmus and strabismus [7].

Early motor, as well as intellectual, development is delayed, with most patients starting to walk between 2 and 3 years and to talk after 3 years of age.
Severe myalgia, weakness and massive myoglobinuria, presumably following unspecified viral infections, are reported in an increasing number of patients. Para-infectious rhabdomyolysis, which is rare in the general population [9], may be a common environmentally-triggered feature of the CCFDN syndrome, possibly related to an
On physical examination, all patients are of small stature and most are also of low weight. Head circumference is reduced; however, its ratio to height is normal. Facial dys-

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inability of the transcription machinery to meet the higher demands imposed by the febrile condition. Patients and care-providers should be aware of this complication and seek prompt medical attention to prevent acute kidney failure.

Diagnostic methods

The clinical diagnosis is based on observation of the symptoms and manifestations described above, supported by electrophysiological and brain imaging studies. The definitive diagnosis is molecular, based on homozygosity for the splicing mutation in intron 6 of the CTDP1 gene. The test is a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay, relying on the abolition of an NlaIII restriction site by the mutation [3]. Molecular testing based on linkage analysis may be problematic, due to the recent origin of the mutation on a common haplotype background and the persisting presence of the ancestral haplotype on normal chromosomes in the same population [3].
Sex hormone (testosterone and oestrogen) levels are decreased. External secondary sexual characteristics appear normal; however most adult female patients have irregular menstrual cycles progressing to secondary amenorrhea at age 25–35 years. Bone mineral density is reduced both in compact and trabecular bone.

Aetiology

CCFDN is a genetically homogeneous condition, where all patients are homozygous for the same ancestral mutation. The CCFDN gene maps to 18qter [1]. The recently identified mutation is a C>T substitution 389 bp downstream of the exon 6/intron 6 junction of the Carboxy-Ter-

minal Domain Phosphatase 1 (CTDP1) gene [3]. The

mutation occurs in an antisense Alu element and triggers a rare mechanism of aberrant splicing: it creates a perfect donor splice site which, in turn, activates an upstream cryptic acceptor site, leading to the insertion of 95 nucleotides of the intronic Alu sequence into the processed CTDP1 transcript. The insertion causes a shift in the reading frame and a premature termination codon. Since both normal and aberrant splicing occur in CCFDN cells [3], the mutation is predicted to lead to partial protein deficiency. The CTDP1 gene encodes a protein phosphatase, commonly referred to as FCP1, whose only known substrate is the phosphorylated serine residues of the carboxyterminal domain (CTD) of the largest subunit of RNA polymerase II [10]. RNA polymerase II is responsible for the transcription of protein-encoding genes in eukaryotic cells, and the level of CTD phosphorylation is considered to be a key mechanism for the regulation of gene expression [11]. In addition to, and independent of its enzyme activity, FCP1 has been proposed to play other roles in transcription: as a positive transcription regulator, an elongation factor, a factor counteracting the Srb-10 complex (which down-regulates the expression of cell cycle and developmentally regulated genes), and in the mechanisms of splicing. At this stage, it is unclear which molecular function(s) is most affected by the CCFDN mutation and thus responsible for the disease phenotype.
So far, CCFDN is known to affect patients of Roma (Gypsy) ethnicity, with the history of this population helping to identify the molecular basis of the disease. It is logical to expect that there are affected individuals of different ethnicity displaying similar phenotypic features and that these patients would have other mutations of the same gene. In such cases, sequencing analysis of CTDP1, as well as of the SIL1 gene recently found to be mutated in Marinesco-Sjögren syndrome (MSS) [12,13], will not only help the diagnostic investigations in the specific affected families, but will also contribute to understanding the molecular pathogenesis of the two disorders. It is advisable to make cultured cells (skin fibroblasts, lymphoblastoid cells, myoblasts, or Schwann cells) available for molecular studies, since the mutation(s) can be predicted to cause partial deficiency, and are thus likely to occur in introns and regulatory sequences and to require RNA- based analysis for elucidation.

Differential diagnosis

In early infancy, when most features of the CCFDN syndrome have yet to appear, a differential diagnosis to be considered is galactokinase deficiency, an inborn error of metabolism common among the Roma which, if untreated, leads to the development of cataracts in the first weeks of life [14,15]. The two conditions can be distinguished by specialised ophthalmological examination, searching for the additional ocular manifestations of CCFDN (described above), as well as by testing for the two founder mutations – in the CTDP1 and GALK1 genes.

The major differential diagnosis is MSS [12,13,16,17], whose phenotypic features partly overlap those of CCFDN [6,8] (Table 1). While substantial clinical heterogeneity exists among patients diagnostically labelled as MSS, mutations in the SIL1 gene on chromosome 5q seem to result in a relatively homogeneous phenotype, characterised by congenital cataracts, developmental delay, severe ataxia and cerebellar atrophy, and chronic myopathy [12,13]. The heterogeneity is still incompletely resolved,
Regardless of the need for understanding the specific molecular pathogenesis, it is already clear that CCFDN affects basic cellular mechanisms of gene expression and their developmental regulation. The disorder belongs to the (currently) small group of "transcription syndromes" and, at present, is the only known defect directly involving RNA polymerase II-mediated gene expression.

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Table 1: Clinical criteria in differential diagnosis of Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN) and Marinesco- Sjögren syndrome (MSS)

  • SYMPTOMS
  • CCFDN
  • MSS

  • Microcornea, microphthalmos, micropupils Yes
  • No

Developmental delay Small stature
Yes Yes
Yes Yes
Facial dysmorphism Peripheral neuropathy Ataxia
Yes, mild, late childhood Yes, hypomyelinating Rare, mild*
No Rare, variable type Severe cerebellar

  • Cerebellar atrophy
  • Brain MRI
  • Cerebral atrophy*

  • Myopathy
  • Acute para-infectious rhabdomyolysis* Chronic

Cognitive deficit Hypogonadism
Mild* Mild*
Variable degree Variable in degree and origin (hypo/hypergonadotrophic)

* Manifestations whose frequency and nature require further characterisation.

with some "typical", as well as "atypical" MSS cases failing to show linkage to 5q and/or mutations in SIL1 [13,18].
40 years of age). While the most disabling manifestations involving the eyes and the peripheral nervous system are not curable, they are manageable, allowing an acceptable quality of life and performance of daily activities.

Genetic counselling

The disorder is autosomal recessive, with a Mendelian risk of 25% for subsequent pregnancies. Given the high frequency of the mutation, and the endogamous tradition of the affected population, discussions of consanguinity are irrelevant and can be counterproductive. Most affected families are very receptive to genetic counselling and predictive testing.

Unresolved questions

Clinical features

The nature of the pathological changes in the central nervous system is still to be resolved. At present, it is unclear whether the brain and spinal cord atrophy observed on MRI result from primary hypomyelination, as is the case for the peripheral nervous system [2,5] or secondary degenerative processes. Furthermore, the recently reported diffusion tensor MRI evidence of axonal loss in the brain [8] needs to be confirmed in larger groups of patients. The nature of the endocrine abnormalities is also poorly defined. Although the hypogonadism seen in CCFDN patients has been classified as hypogonadotrophic [2], the evidence is not conclusive, and the problem may in fact reside in changes in the expression profile of the gonads. The frequency of rhabdomyolysis in CCFDN patients and the nature of the factors triggering this severe complication remain to be determined; careful collection of case histories and patient follow-up will provide this information.

Prenatal diagnosis

Prenatal analysis is best performed by testing for the disease mutation on DNA extracted from chorionic villus samples.

Management

Management includes the treatment of cataracts, and rehabilitation and corrective surgery for the peripheral neuropathy. Eye surgery may be complicated by strong postoperative inflammatory reactions, as well as a strong unspecific foreign-body reaction to contact lenses and intra-ocular lenses, with a generally better tolerance to intra-ocular lenses [7]. CCFDN patients are prone to developing severe and potentially life-threatening complications during anaesthesia, such as pulmonary oedema, inspiratory stridor, malignant hyperthermia and epileptic seizures [6,7] and thus need close monitoring and possibly intensive post-operative care.

Molecular mechanisms

Further studies are needed to elucidate the specific molecular processes that lead to the phenotypic manifestations of CCFDN. The mutated protein is believed to be of universal importance for the regulation of RNA polymerase II activity and the CCFDN mutation is expressed in all cell types investigated, yet the clinical phenotype is limited to just a few of them. This cell specificity, possibly resulting from differences in back-up mechanisms and in the relative contribution of other CTD phosphatases to RNA polymerase II regulation, is a major question, resolution

Prognosis

The recent recognition of CCFDN as a novel disease entity, and the lack of prospective follow-up does not allow an evidence-based prognosis regarding life expectancy. Current observations indicate that patients survive well into adulthood (the oldest known cases being over

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galactokinase deficiency in Gypsies. Am J Hum Genet 1999, 65:1299-1307.

of which will not only help understanding of the disease itself, but could also contribute to unravelling fundamental mechanisms of the regulation of gene expression.

15. Hunter M, Heyer E, Austerlitz F, Angelicheva D, Nedkova V, Briones
P, Gata A, de Pablo R, Laszlo A, Bosshard N, Gitzelman R, Tordai A, Kalmar L, Szalai C, Balogh I, Lupu C, Corches A, Popa G, Perez-

Lezaun A, Kalaydjieva L: The P28T mutation in the GALK1 gene accounts for galactokinase deficiency in Roma (Gypsy) patients across Europe. Pediatr Res 2002, 51:602-606.

16. Marinesco G, Draganesco S, Vasiliu D: Nouvelle maladie familiale

caracterisée par une cataracte congénitale et un arret du développement somato-neuro-psychique. Encephale 1931, 26:97-109.
17. Sjögren T: Hereditary congenital spino-cerebellar ataxia accompanied by congenital cataract and oligophrenia. Con-

finia Neurol 1950, 10:293-308.

18. Lagier-Tourenne C, Tranebjerg L, Chaigne D, Gribaa M, Dolfus H, Silvestri G, Betard C, Warter JM, Koenig M: Homozygosity mapping

of Marinesco-Sjögren syndrome to 5q31. Eur J Hum Genet 2003, 11:770-778.

References

  • 1.
  • Angelicheva D, Turnev I, Dye D, Chandler D, Thomas PK, Kalaydjieva

L: Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a novel developmental disorder in Gypsies maps to 18qter. Eur J Hum Genet 1999, 7:560-566.

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    Hodgkin Lymphoma SUPPLEMENTARY APPENDIX Whole exome sequencing in families at high risk for Hodgkin lymphoma: identification of a predisposing mutation in the KDR gene Melissa Rotunno, 1 Mary L. McMaster, 1 Joseph Boland, 2 Sara Bass, 2 Xijun Zhang, 2 Laurie Burdett, 2 Belynda Hicks, 2 Sarangan Ravichandran, 3 Brian T. Luke, 3 Meredith Yeager, 2 Laura Fontaine, 4 Paula L. Hyland, 1 Alisa M. Goldstein, 1 NCI DCEG Cancer Sequencing Working Group, NCI DCEG Cancer Genomics Research Laboratory, Stephen J. Chanock, 5 Neil E. Caporaso, 1 Margaret A. Tucker, 6 and Lynn R. Goldin 1 1Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; 2Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; 3Ad - vanced Biomedical Computing Center, Leidos Biomedical Research Inc.; Frederick National Laboratory for Cancer Research, Frederick, MD; 4Westat, Inc., Rockville MD; 5Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; and 6Human Genetics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA ©2016 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2015.135475 Received: August 19, 2015. Accepted: January 7, 2016. Pre-published: June 13, 2016. Correspondence: [email protected] Supplemental Author Information: NCI DCEG Cancer Sequencing Working Group: Mark H. Greene, Allan Hildesheim, Nan Hu, Maria Theresa Landi, Jennifer Loud, Phuong Mai, Lisa Mirabello, Lindsay Morton, Dilys Parry, Anand Pathak, Douglas R. Stewart, Philip R. Taylor, Geoffrey S. Tobias, Xiaohong R. Yang, Guoqin Yu NCI DCEG Cancer Genomics Research Laboratory: Salma Chowdhury, Michael Cullen, Casey Dagnall, Herbert Higson, Amy A.
  • Integrated Analysis of Human Influenza a (H1N1) Virus Infection

    Integrated Analysis of Human Influenza a (H1N1) Virus Infection

    BIOCELL Tech Science Press 2021 45(4): 885-899 Integrated analysis of human influenza A (H1N1) virus infection- related genes to construct a suitable diagnostic model WENBIAO CHEN; KEFAN BI; JINGJING JIANG; XUJUN ZHANG; HONGYAN DIAO* State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China Key words: Human influenza A, H1N1 virus, Gene, Diagnosis model Abstract: The genome characteristics and structural functions of coding proteins correlate with the genetic diversity of the H1N1 virus, which aids in the understanding of its underlying pathogenic mechanism. In this study, analyses of the characteristic of the H1N1 virus infection-related genes, their biological functions, and infection-related reversal drugs were performed. Additionally, we used multi-dimensional bioinformatics analysis to identify the key genes and then used these to construct a diagnostic model for the H1N1 virus infection. There was a total of 169 differently expressed genes in the samples between 21 h before infection and 77 h after infection. They were used during the protein– protein interaction (PPI) analysis, and we obtained a total of 1725 interacting genes. Then, we performed a weighted gene co-expression network analysis (WGCNA) on these genes, and we identified three modules that showed significant potential for the diagnosis of the H1N1 virus infection. These modules contained 60 genes, and they were used to construct this diagnostic model, which showed an effective prediction value. Besides, these 60 genes were involved in the biological functions of this infectious virus, like the cellular response to type I interferon and in the negative regulation of the viral life cycle.
  • Investigating Trait Variability of Gene Co-Expression Network Architecture in Brain by Manipulating Genomic Signatures of Schizophrenia Risk

    Investigating Trait Variability of Gene Co-Expression Network Architecture in Brain by Manipulating Genomic Signatures of Schizophrenia Risk

    bioRxiv preprint doi: https://doi.org/10.1101/2021.05.04.442668; this version posted May 7, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Investigating trait variability of gene co-expression network architecture in brain by manipulating genomic signatures of schizophrenia risk Eugenia Radulescua,1, Qiang Chena, Giulio Pergolaa,b, Nicholas J Eaglesa, Joshua M Stolza, Joo Heon Shina, Thomas M Hydea,c,d, Joel E Kleinmana,c, Daniel R Weinbergera,c,d,e,f,1 Affiliations: a. Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA b. Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy c. Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA d. Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA e. Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA f. McKusick-Nathans Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA 1Address correspondence to: Daniel R. Weinberger Lieber Institute for Brain Development 855 North Wolfe Street Baltimore, Maryland 21205 410-955-1000 ([email protected]) Eugenia Radulescu Lieber Institute for Brain Development 855 North Wolfe Street Baltimore, Maryland 21205 410-955-1000 ([email protected]) 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.05.04.442668; this version posted May 7, 2021.
  • Deoxyribonucleic Acid Copy Number Aberrations in Vasospastic Angina Patients Using an Array Comparative Genomic Hybridization

    Deoxyribonucleic Acid Copy Number Aberrations in Vasospastic Angina Patients Using an Array Comparative Genomic Hybridization

    ORIGINAL ARTICLE Print ISSN 1738-5520 / On-line ISSN 1738-5555 DOI 10.4070/kcj.2011.41.7.385 Copyright © 2011 The Korean Society of Cardiology Open Access Deoxyribonucleic Acid Copy Number Aberrations in Vasospastic Angina Patients Using an Array Comparative Genomic Hybridization Suk Min Seo, MD1, Yoon Seok Koh, MD1, Hae Ok Jung, MD1, Jin Soo Choi, MD2, Pum Joon Kim, MD1, Sang Hong Baek, MD1, Ho-Joong Youn, MD1, Kweon-Haeng Lee, MD3, and Ki-Bae Seung, MD1 1Cardiovascular Center and Cardiology Division, 2Catholic Neuroscience Center, 3Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Korea ABSTRACT Background and Objectives: Vasospastic angina (VA) is a specific type of coronary artery disease and develops as a result of coronary artery spasm. Recently, a few studies have revealed that VA caused by coronary artery spasm is related to genetic traits. The objective of this study was to use the recently developed technique of array comparative genomic hybridization (CGH) to screen the genetic aberrations of VA. Subjects and Methods: To identify candidate genes that might be causally involved in the pathogenesis of VA, genomic deoxyribonucleic acids were extracted from whole blood of 28 patients with VA who presented at Department of Cardiology at Seoul St. Mary’s Hospital, Seoul, Korea. The copy number profiles of these patients was then analyzed using array CGH and reverse transcriptase (RT) quantitative polymerase chain reaction (PCR). Results: Array CGH revealed gains in 31 different regions, with losses in the 4q35.2, 7q22.1, 10q26.3, 15q11.2, 16p13.11, 17p11.2 and 19q13.3 regions (more than 32% aberration in these regions).
  • Datasheet: VPA00440 Product Details

    Datasheet: VPA00440 Product Details

    Datasheet: VPA00440 Description: RABBIT ANTI FCP1 Specificity: FCP1 Format: Purified Product Type: PrecisionAb™ Polyclonal Isotype: Polyclonal IgG Quantity: 100 µl Product Details Applications This product has been reported to work in the following applications. This information is derived from testing within our laboratories, peer-reviewed publications or personal communications from the originators. Please refer to references indicated for further information. For general protocol recommendations, please visit www.bio-rad-antibodies.com/protocols. Yes No Not Determined Suggested Dilution Western Blotting 1/1000 PrecisionAb antibodies have been extensively validated for the western blot application. The antibody has been validated at the suggested dilution. Where this product has not been tested for use in a particular technique this does not necessarily exclude its use in such procedures. Further optimization may be required dependant on sample type. Target Species Human Species Cross Reacts with: Mouse Reactivity N.B. Antibody reactivity and working conditions may vary between species. Product Form Purified IgG - liquid Preparation Rabbit polyclonal antibody purified by affinity chromatography Buffer Solution Phosphate buffered saline Preservative 0.09% Sodium Azide (NaN ) Stabilisers 3 Immunogen KLH conjugated synthetic peptide corresponding to amino acid 247-276 of human FCP1 External Database Links UniProt: Q9Y5B0 Related reagents Entrez Gene: 9150 CTDP1 Related reagents Synonyms FCP1 Page 1 of 2 Specificity Rabbit anti Human FCP1 antibody recognizes FCP1, also known as RNA polymerase II subunit A C-terminal domain phosphatase, serine phosphatase FCP1a or transcription factor IIF-associating CTD phosphatase 1. The CTDP1 gene encodes a protein which interacts with the carboxy-terminus of the RAP74 subunit of transcription initiation factor TFIIF, and functions as a phosphatase that processively dephosphorylates the C-terminus of POLR2A (a subunit of RNA polymerase II), making it available for initiation of gene expression.
  • Chromosome 18 Gene Dosage Map 2.0

    Chromosome 18 Gene Dosage Map 2.0

    Human Genetics (2018) 137:961–970 https://doi.org/10.1007/s00439-018-1960-6 ORIGINAL INVESTIGATION Chromosome 18 gene dosage map 2.0 Jannine D. Cody1,2 · Patricia Heard1 · David Rupert1 · Minire Hasi‑Zogaj1 · Annice Hill1 · Courtney Sebold1 · Daniel E. Hale1,3 Received: 9 August 2018 / Accepted: 14 November 2018 / Published online: 17 November 2018 © Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract In 2009, we described the first generation of the chromosome 18 gene dosage maps. This tool included the annotation of each gene as well as each phenotype associated region. The goal of these annotated genetic maps is to provide clinicians with a tool to appreciate the potential clinical impact of a chromosome 18 deletion or duplication. These maps are continually updated with the most recent and relevant data regarding chromosome 18. Over the course of the past decade, there have also been advances in our understanding of the molecular mechanisms underpinning genetic disease. Therefore, we have updated the maps to more accurately reflect this knowledge. Our Gene Dosage Map 2.0 has expanded from the gene and phenotype maps to also include a pair of maps specific to hemizygosity and suprazygosity. Moreover, we have revamped our classification from mechanistic definitions (e.g., haplosufficient, haploinsufficient) to clinically oriented classifications (e.g., risk factor, conditional, low penetrance, causal). This creates a map with gradient of classifications that more accurately represents the spectrum between the two poles of pathogenic and benign. While the data included in this manuscript are specific to chro- mosome 18, they may serve as a clinically relevant model that can be applied to the rest of the genome.